Peptide nucleic acid (PNA) modified with unnatural nucleobases enables the formation of a highly stable triplex with a double-stranded RNA at physiological pH. In this communication, we evaluated kinetics and thermodynamics of PNA/RNA triplex formation as a function of both pH and temperature. Protonation entropy was found to be the major factor responsible for the destabilization of the triplex and for the progressive decrease in the association rate at more basic pHs.
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http://dx.doi.org/10.1039/c6cp05013a | DOI Listing |
NAR Genom Bioinform
December 2024
Department of Chemistry, Ben Gurion University of the Negev, Beer Sheva, 8410501, Israel.
We have subjected several analogs of DNA that have been widely used as antisense oligonucleotide (ASO) inhibitors of gene expression to comparative molecular dynamics (MD) calculations of their ability to form duplexes with DNA and RNA. The analogs included in this study are the phosphorothioate (PS), peptide nucleic acid (PNA), locked nucleic acid (LNA), morpholino nucleic acid (PMO), the 2'-OMe, 2'-F, 2'-methoxyethyl (2'-MOE) and the constrained cET analogs, as well as the natural phosphodiester (PO) as control, for a total of nine structures, in both XNA-DNA and XNA-RNA duplexes. This is intended as an objective criterion for their relative ability to duplex with an RNA complement and their comparative potential for antisense applications.
View Article and Find Full Text PDFBioorg Med Chem
December 2024
Natural Products Research Institute, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea. Electronic address:
Targeting the genes regulate the lineage commitment of human mesenchymal stem cells (hMSCs) to adipocytes provides a promising strategy for addressing obesity. In this study, we investigated the therapeutic potential of cell-penetrating anti-sense peptide nucleic acids (PNAs) designed to enhance solubility and hybridization properties, specifically targeting sulfatase 2 (SULF2), a potential reciprocal regulator of adipocyte and osteoblast differentiation in hMSCs. Cell-penetrating modified PNA oligomers effectively inhibit SULF2 gene transcription, leading to significant reductions in adiponectin protein synthesis and intracellular lipid droplet accumulation during adipogenesis in human bone marrow-derived MSCs (hBM-MSCs).
View Article and Find Full Text PDFBioorg Med Chem Lett
January 2025
Natural Products Research Institute, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea. Electronic address:
Maedica (Bucur)
September 2024
Faculty of Medicine, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania.
Background And Objectives: The importance of hematological parameters has started to be explored with increased interest in many fields lately, with different studies finding an association between those parameters and inflammatory status, atherosclerosis, comorbidities, malnutrition, neoplasia and even a faster progression of chronic kidney disease (CKD). On the other hand, CKD itself presents as an inflammatory condition, in which a lot of pathways are modified and the response to an infectious agent could be less than expected. Regarding the latter aspect, in this study we aim to explore the differences between the hematologic response during a lower versus upper urinary tract infection in patients with CKD.
View Article and Find Full Text PDFInt J Pharm
January 2025
Department of Pharmacy, University of Naples Federico II, via D. Montesano 49, Naples 80131, Italy.
Cancer immunotherapy is focused on stimulating the immune system against cancer cells by exploiting immune checkpoint mechanisms. PD-1/PD-L1 is one of the most known immune checkpoints due to the widespread upregulation of the Programmed Death Ligand 1 (PD-L1) transmembrane protein in cancer tissues. Accordingly, taking advantage of the ability of oncolytic adenoviruses (OAd) to specifically infect and kill tumor cells over healthy ones, here, we developed a targeted delivery platform based on OAd to selectively deliver in cancer cells an antisense peptide nucleic acid (PNA) targeting the PD-L1 mRNA.
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